Acromegaly: pathogenesis & treatment
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Acromegaly is a multi-system disorder whose etiology is most often traced back to a growth hormone-secreting pituitary adenoma (PA). Growth hormone (GH) secretion promotes insulin-like growth factor 1 (IGF-1) release from peripheral tissues, leading to the clinical manifestations of acromegaly. Current treatment methods for acromegaly include surgery, medical therapy, and radiation therapy. The goals of acromegaly treatment are to reduce GH levels and IGF-1 levels to age/sex-normalized levels, relieve comorbidities, normalize mortality rate, and to remove the pituitary mass causing high hormone levels. This study aims to provide a comprehensive review of current treatment methods and an analysis of novel therapies for treatment of acromegaly. The primary treatment method of acromegaly is surgery due to limited complications, relatively low cost, and remission in the majority of cases. However, surgery is not an effective treatment method for invasive macroadenomas with extension into the intracranial space. Medical therapies such as dopamine agonists (DAs) and somatostatin receptor ligands (SRLs) are effective at reducing GH and IGF-1 levels and may have anti-tumor effects. However, DAs are only effective at treating minor elevations in GH and IGF-1 levels and SRLs may cause hyperglycemia after prolonged treatment. In contrast to DAs and SRLs, Pegvisomant does not have anti-tumor effects, but it is more effective at reducing GH and IGF-1 levels. The disadvantages of Pegvisomant are the possibility of irreversible liver damage and the overwhelming cost of treatment. Stereotactic radiosurgery (SRS) is another mode of treatment for acromegaly, however, there are many disadvantages to SRS including prolonged latency period, hypopituitarism, radio-necrosis of normal brain tissue, and secondary tumor formation. Novel therapies for acromegaly include antisense drugs and modified botulin neurotoxins. Despite the success of antisense drugs and modified botulin neurotoxins in animal models, greater research is required prior to application in human clinical trials. Gene therapy is an emerging treatment method for acromegaly and proper manipulation of viral immunogenic effects could prove as a successful treatment for large macroadenomas, invasive PAs, and recurrent PAs. Despite the success of surgery in treating microadenomas and noninvasive macroadenomas, therapeutic alternatives must be explored to treat invasive PAs, macroadenomas, and recurrent PAs. Future research in immunotherapies and gene therapies may provide greater insight into the development of more effective and less invasive treatment methods for acromegaly.